gemcitabine, carboplatin or paclitaxel plus radiation therapy in treating patients with stage iiia or iiib non-small cell lung cancer

Conditions: Lung Cancer

Summary: rationale: drugs used in chemotherapy, such as gemcitabine, carboplatin, and paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. radiation therapy uses high-energy x-rays to damage tumor cells. combining radiation therapy with chemotherapy may kill more tumor cells. purpose: phase i trial to study the effectiveness of combining combination chemotherapy with radiation therapy in treating patients who have stage iiia or stage iiib non-small cell lung cancer.

objectives: * determine the maximum tolerated dose (mtd) of gemcitabine when administered with carboplatin and thoracic radiotherapy followed by adjuvant gemcitabine and carboplatin in patients with stage iiia or iiib non-small cell lung cancer. * determine the mtd of gemcitabine and paclitaxel when administered with thoracic radiotherapy followed by adjuvant gemcitabine and carboplatin in these patients. outline: this is a multicenter, dose-escalation study of gemcitabine and paclitaxel. patients are sequentially assigned to 1 of 3 treatment regimens. * regimen a: patients receive gemcitabine iv over 30-60 minutes on days 1, 8, 22, 29, and 43 and thoracic radiotherapy daily 5 days a week for 7 weeks beginning on day 1. * regimen b (closed to accrual as of 5/13/03): patients receive gemcitabine and thoracic radiotherapy as in regimen a and carboplatin iv over 30 minutes on days 1, 8, 22, 29, and 43. * regimen c: patients receive gemcitabine and thoracic radiotherapy as in regimen a and paclitaxel iv over 1 hour on days 1, 8, 22, 29, and 43. at 3 weeks after completion of chemoradiotherapy, all patients receive adjuvant gemcitabine iv over 30-60 minutes on days 71, 78, 92, and 99 and carboplatin iv over 30 minutes on days 71 and 92. the first 6 patients enrolled receive regimen a to determine the safety of the initial dose of gemcitabine. after completion of regimen a, cohorts of 3-6 patients receive escalating doses of gemcitabine in regimen b (closed to accrual as of 5/13/03) until the maximum tolerated dose (mtd) is determined. in a separate sequence, cohorts of 3-6 patients receive alternating escalating doses of gemcitabine and paclitaxel in regimen c until the mtd is determined. the mtd is defined as the dose preceding that at which at least 3 of 6 patients experience dose-limiting toxicity. patients are followed at 3 months, 6 months, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter. projected accrual: a maximum of 78 patients will be accrued for this study within 29 months.

Eligibility criteria:
disease characteristics: * histologically or cytologically confirmed loco-regionally advanced non-small cell lung cancer meeting one of the following staging criteria: * medically inoperable stage iiia * unresectable stage iiia or iiib * measurable disease on three-dimensional planning ct scan * no post-resection intrathoracic tumor recurrence * no pleural effusion on chest x-ray except those occurring after attempted thoracotomy or other invasive thoracic procedure * no evidence of small cell histology * no evidence of hematogenous or distant metastases patient characteristics: age: * not specified performance status: * zubrod 0-1 life expectancy: * not specified hematopoietic: * platelet count at least 100,000/mm\^3 * absolute granulocyte count at least 2,000/mm\^3 * hemoglobin at least 8.0 g/dl hepatic: * bilirubin no greater than 1.5 mg/dl * serum glutamate oxaloacetate transaminase (sgot) no greater than 1.5 times upper limit of normal (unless caused by documented benign disease) renal: * creatinine no greater than 1.5 mg/dl cardiovascular: * no myocardial infarction within the past 6 months * no symptomatic heart disease, including angina, congestive heart failure, or uncontrolled arrhythmia pulmonary: * forced expiratory volume (fev)_1 greater than 1,000 ml other: * no other invasive malignancy within the past 3 years except nonmelanoma skin cancer * no weight loss of more than 10% in 3 months prior to diagnosis * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception prior concurrent therapy: biologic therapy: * not specified chemotherapy: * no prior chemotherapy endocrine therapy: * not specified radiotherapy: * no prior thoracic or neck radiotherapy surgery: * see disease characteristics * no prior complete or subtotal tumor resection

Keywords: stage iiia non-small cell lung cancer stage iiib non-small cell lung cancer